Major depressive disorder Mental and Behavioural Disorders Depressive episode, Recurrent depressive disorder
Conditions
Interventions
Participants will be randomised 1:1 to either active drug or placebo. This will be carried out using a web-based randomisation system. Eligible participants will be randomly allocated to receive eithe
Sponsors
Cambridgeshire and Peterborough NHS Foundation Trust
University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For a detailed description of inclusion criteria please refer to protocol section 10.1 1. Provided written informed consent 2. Between the age of 18 to 60 years inclusive 3. Meets the DSM-5 diagnostic criteria for MDD (International Classification of Diseases (ICD)-code F32.x and F33.x), without psychotic features, as confirmed by the M.I.N.I 7.0 (Mini International Neuropsychiatric Interview 7.0) 4. Has Hamilton Depression Rating Scale (HDRS) score of > = 17 5. BMI between 18 and 36 kg/m2 inclusive 6. Currently being treated with one antidepressant monoaminergic drug (e.g. SSRI, SNRI, TCA) at an adequate dose, and for at least 6 weeks and for a maximum of 24 months 7. Must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed 8. Agree to practice highly effective method of birth control as stated in the protocol 9. A woman of childbearing potential must have a negative serum pregnancy test at screening 10. Agree not to donate eggs or sperm from start of dosing and for at least 3 months after receiving the last dose of study drug
Exclusion criteria
Exclusion criteria: For a detailed description of exclusion criteria please refer to protocol section 10.2 1. Has a primary DSM-5 diagnosis of posttraumatic stress disorder 2. Has failed more than 3 treatments despite an adequate dose and duration, in the last 24 months 3. Loss of function allele at one or both of two SNPs on the P2RX7 gene: rs3751143 (1487 A> C) and rs1653624 (1703 T> A) 4. Has a current or recent history of clinically significant suicidality 5. Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening 6. Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy) 7. Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder) 8. Has used: 8.1. Monoamine oxidase inhibitors (MAOIs) within 12 weeks before screening 8.2. Within 6 weeks prior to enrolment use of other antidepressant drugs not belonging to the allowed classes of SSRI, SNRI, or TCA. 9. Is currently treated with antipsychotic drugs (D2-antagonists; except for low-dose quetiapine), lithium, other mood stabilizers or opiates 10. Unable to complete MRI scans 11. Has current signs/symptoms of liver or renal insufficiency, diabetes mellitus (type I and II), hypothyroidism or hyperthyroidism without stable treatment, or other significant and uncontrolled medical conditions 12. Is a woman who is pregnant or breastfeeding 13. Is a man who plans to conceive a child while enrolled in this study or within 3 months after the last dose of IMP 14. Has a history of malignancy within 5 years before screening 15. Has received an investigational drug/vaccines, used an invasive investigational medical device within 60 days before the planned first dose of IMP, or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in any drug or non-drug interventional study 16. Venous blood concentration of C-reactive protein, measured by high sensitivity assay (hs-CRP) less than 1 mg/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Depression symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and week 8 (Visit 4) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Depressive symptom severity measured using: 1.1. Clinician-reported scales MINI and HDRS17 at screening and baseline and MADRS at weeks 2 and 5 1.2. Participant-reported questionnaires SHAPS, QIDS-SR16, GAD-7, Chalder Fatigue Questionnaire, Perceived Stress Scale, Beck’s Depression Inventory and Childhood Trauma Questionnaire at baseline and over time at every visit until week 8 2. Suicidality assessed using the Columbia Suicidal Severity Rating Scale assessed at every clinic visit (screening, baseline visit 1, visit 2, visit 3, visit 4 and follow up visit 5) 3. Cognitive function assessed using computerised cognitive tasks designed to test for emotion-independent functions, emotion-dependent functions and sustained attention at baseline and over time at every visit until week 8 4. Stress assessed by cortisol levels in the saliva before baseline and before the last dose 5. Fatigue and activity measured using an activity monitor at baseline and over time until week 8 6. Functions of the autonomic nervous system measured by variability in heart rate at baseline and week 8 7. Brain structure and function assessed by functional MRI scan at baseline and week 8 8. Peripheral immunophenotypes measured by various biomarker assays looking at proportions of immune cells, level of cytokine release, CRP protein (marker of inflammation) levels, and gene expression at baseline and week 8 | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactElizabeth;Rachel Chong;Lee
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Outcome results
None listed